It is the purpose of this proposal to study the physiology of the gonadotropin releasing hormone, LHRH, in man utilizing both in vivo and in vitro approaches. LHRH deficient males with idiopathic hypogonadotropic hypogonadism are able to synthesize and release gonadotropins which can elicit physiologic gonadal responses when administered LHRH exogenously. Employing an adaptation of the portable infusion pump previously used to administer insulin to diabetics, we have been able to administer low-dose, pulsatile LHRH to these men in long-term studies. This system allows administration of LHRH to this ideal experiment of nature in a controlled fashion and permits systematic variation of the dose and frequency of the LHRH program. The effects of such variations upon the ratio of gonadotropin secretion and the effect of these varying ratios upon gonadal secretion in turn, can be undertaken with this model for the first time. Additionally, the pituitary effects of a variety of steroidal and non-steroidal modulators of the Reproductive Endocrine system can be directly examined. A dispersed, perifused rat pituicyte system has also been developed which will permit examination of LHRH-stimulated gonadotropin release in the absence of endogenous gonadal secretion. Employing a combination of these two approaches, each with its unique advantage should provide useful insight into the role of pulsatile LHRH in gonadotropin secretion, its modification and physiologic control.